Comprehensive metabolomic/lipidomic characterization of patients with mitochondrial ATP synthase, short-chain acyl-CoA dehydrogenase and combined variant deficiencies
Rattachement africain : cz, sk. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Objective: This study aims to characterize the metabolic alterations in patients with inherited mitochondrial enzymopathies. We focused on wide-coverage targeted metabolomic, organic acid and lipidomic analyses of patients with TMEM70 deficiency (TMEM70d), short-chain acyl-CoA dehydrogenase deficiency (SCADd), and individuals with both deficiencies (TMEM70d-SCADd). Methods: Serum and urine samples were collected from patients with TMEM70d (n = 13), SCADd (n = 11), TMEM70d-SCADd (n = 3), and controls (n = 38). Analyses were conducted using high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Univariate and multivariate statistical evaluation was performed to identify significant metabolic differences between patient groups and controls. Results: Distinct metabolic profiles were observed in urine and serum samples of patients with TMEM70d, SCADd, and TMEM70d-SCADd compared to controls. Urinary metabolomics revealed significant elevations in butyrylcarnitine and metabolites related to branched-chain amino acid degradation in SCADd and TMEM70d-SCADd patients. Serum metabolomic analysis indicated alterations in pyruvate metabolism, citric acid cycle intermediates, and acylcarnitine metabolism in TMEM70d and TMEM70d-SCADd patients. Lipidomic analysis showed decreased levels of glycerophospholipids and sphingolipids across all patient groups. Conclusion: Patients with TMEM70d, SCADd, and TMEM70d-SCADd exhibit distinct metabolic signatures characterized by disturbances in energy metabolism, amino acid degradation, and lipid homeostasis. The combination of TMEM70d and SCADd leads to synergistic metabolic effects, emphasizing the importance of comprehensive metabolic profiling in understanding complex mitochondrial disorders and identifying potential biomarkers for diagnosis and treatment monitoring.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Comprehensive metabolomic/lipidomic characterization of patients with mitochondrial ATP synthase, short-chain acyl-CoA dehydrogenase and combined variant deficiencies
- Date Crossref
- 01/02/2025
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
-
Palacký University Olomouc pays non établi dans la noticeUniversité ou école supérieure
-
University Hospital Olomouc Department of Clinical Biochemistry pays non établi dans la noticeÉtablissement de santé
-
University of Pavol Jozef Šafárik pays non établi dans la noticeUniversité ou école supérieure
-
Charles University pays non établi dans la noticeUniversité ou école supérieure
-
Faculty of Medicine and Dentistry Laboratory for Inherited Metabolic Disorders pays non établi dans la noticeUniversité ou école supérieure
-
Department of Laboratory Medicine pays non établi dans la noticeStructure de recherche
-
National Institute of Children's Diseases Department of Pediatrics pays non établi dans la noticeStructure de recherche
-
Children's Faculty Hospital Metabolic Outpatient Clinic pays non établi dans la noticeUniversité ou école supérieure
-
Second Faculty of Medicine pays non établi dans la noticeUniversité ou école supérieure
Palacký University Olomouc, Department of Clinical Biochemistry — University Hospital Olomouc et University of Pavol Jozef Šafárik, avec 6 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.